Safety Of Cariprazine Research Articles

Efficacy and Safety Profiles of Antipsychotic Drugs as Viewed by Psychiatrists: A Comparative Analysis of Cariprazine and Risperidone.

Physicians hold the belief that the treatment outcomes and the treatment strategy they eventually adopt is largely determined by the differences in medications. Despite numerous studies focusing on the decision-making processes of psychiatrists, including the choice of antipsychotics when prescribing pharmacotherapy, the impact of therapeutic drug profiling on physicians' decision-making remains poorly comprehended. The aim of this study is to assess the quantitative differences in perceptions of antipsychotics by psychiatrists using cariprazine and risperidone as examples. A total of 79 psychiatrists were interviewed anonymously in St. Petersburg, Russia. The physicians documented the clinical advantages they perceived drugs to possess relative to one another, following a predetermined principle: A B, A=B, A B (2-AC protocol). The comparison is based on eleven parameters that assess the effectiveness and safety of cariprazine or risperidone. It has been hypothesized that the pattern of responses (qualitative difference) and the degree of preference for each drug (quantitative difference) may not align with the data in the original meta-analyses. The perception parameter exhibited a greater difference than anticipated (δ - 0.889), while the threshold for differentiating between the drugs was lower (τ - 1.001). The response pattern only aligned with theory by 44.37%. The dispersion of responses was associated with the length of work experience. The perceived difference between the drugs significantly deviates from the theoretical data, both in terms of strength of perception and pattern (quantitative and qualitative differences).

Therapeutic Appropriateness of Cariprazine in the Management of Schizophrenia: Experts' Opinion using a Delphi Approach.

Schizophrenia is a psychiatric disorder whose therapeutic objectives are aimed at reducing symptoms and improving patient's quality of life. First- and second-generation antipsychotics present numerous side effects. Recently introduced in the treatment of schizophrenia, cariprazine has shown to improve positive and negative symptoms as well as cognitive impairment, with good tolerability. To assess the level of consensus among Italian psychiatrists in relation to the use of cariprazine in the treatment of schizophrenia by using the Delphi technique. A Delphi study was undertaken between January and July 2022. Two questionnaires were consecutively sent to a panel of 97 psychiatrists from all over Italy, of which 81 actively participated, anonymously, in at least one of the two consultations with a sufficiently high response rate (83%). Broad consensus in terms of the efficacy and safety of cariprazine in the treatment of schizophrenia during all phases of the disorder. The young first-episode schizophrenia patient with or without substance abuse seems to be an excellent candidate for cariprazine therapy. In addition, the lack of side effects makes cariprazine a suitable drug for adult and elderly patients with schizophrenia. However, there is still limited experience with the use of cariprazine, along with little knowledge of the most recent real-life data. These results could encourage wider dissemination of evidence-based practices with the final aim of optimizing the clinical use of cariprazine in patients with schizophrenia.

Safety and Tolerability of Cariprazine for the Adjunctive Treatment of Major Depressive Disorder: A Pooled Analysis of Phase 2B and 3 Clinical Trials

AbstractBackgroundCariprazine has been shown to be efficacious in placebo-controlled clinical trials. In this pooled analysis, the safety of cariprazine in patients with major depressive disorder (MDD) with inadequate response to antidepressants was evaluated using data from placebo-controlled studies of up to 8 weeks’ duration and a long-term open-label safety study.MethodsThe safety, tolerability, and efficacy of cariprazine as an adjunctive treatment for patients with MDD with inadequate response to antidepressant alone was assessed in five placebo-controlled studies (two 6-week fixed-dose studies [NCT03738215; NCT03739203] and three 8-week flexible-dose studies [NCT00854100; NCT01715805; NCT01469377]) and one 26-week open-label flexible-dose study (NCT01838876). Fixed doses of cariprazine 1.5 and 3 mg/d and flexible doses of 0.1-4.5 mg/d were evaluated. Safety assessments included adverse event (AE) reporting, clinical laboratory tests, weight and other vital signs, and suicide evaluation with Columbia-Suicide Severity Rating Scale (C-SSRS). Pooled analyses of the incidence of safety endpoints overall and within each treatment arm were performed using the most frequent (modal) daily dose taken by patients during the study.ResultsA total of 2,222 MDD patients with an ongoing antidepressant received treatment with cariprazine, representing 370 patient-years of exposure in placebo-controlled and open-label studies. In the placebo-controlled studies, 1,969 patients were randomized to cariprazine (dose range, 0.1–4.5 mg/d) and 1,108 patients were randomized to placebo. Overall, treatment-emergent AEs occurred in 61% of cariprazine- and 48% of placebo-treated patients; discontinuation due to an AE occurred with 6% of cariprazine- and 2% of placebo-treated patients. The 2 AEs that occurred in at least 5% of cariprazine-treated patients and at a rate at least twice the rate in placebo-treated patients were akathisia (cariprazine=11%; placebo=2%) and restlessness (cariprazine=6%; placebo=2%). Changes in metabolic parameters, including shifts in fasting glucose and lipid parameters, were similar in cariprazine- and placebo-treated patients. In the long-term safety study, mean weight change was 1.6 kg over 6 months. In the placebo-controlled and long-term studies, other safety endpoints including laboratory and C-SSRS assessments of suicidality were generally consistent with the safety profile of cariprazine in approved indications of bipolar disorder and schizophrenia.ConclusionCariprazine is generally safe and well-tolerated in MDD patients with inadequate response to antidepressant monotherapy. Safety analysis of 2,222 cariprazine-treated patients with MDD revealed no new safety signals, and the data is consistent with the currently approved prescribing information.FundingAbbVie

Cariprazine for the Adjunctive Treatment of Major Depressive Disorder: Results of a Randomized Phase 3 Placebo-Controlled Study (Study 301)

AbstractBackgroundPatients with major depressive disorder (MDD) often do not respond to antidepressant (ADT) monotherapy; adjunctive treatment is often used to address this unmet need. Cariprazine (CAR), a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with manic, mixed, or depressive episodes of bipolar I disorder, is under investigation as adjunctive therapy for patients with MDD.MethodsThis randomized, double-blind, phase 3 placebo (PBO)-controlled study assessed the efficacy, safety, and tolerability of CAR 1.5 and 3 mg/d as an adjunct to ADT in adult patients with MDD (18–65 years) and inadequate response to ADT alone (NCT03738215). The primary endpoint was change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impressions (CGI) were also assessed. Treatment response was defined as at least 50% decrease in MADRS total score at week 6.ResultsPatients (n=751) in the modified intent-to-treat population were randomly assigned to CAR 1.5 mg/d+ADT (n=250), CAR 3 mg/d+ADT (n=252), or PBO+ADT (n=249). Mean age was 44.8 years and 73.4% were female; mean baseline total scores were: MADRS=32.5, HAMD-17=25.9, HAM-A= 21.4. Overall, 89.7% of patients completed the study; rates of discontinuation due to adverse events (AEs) and lack of efficacy were 3.6% and 0.5%, respectively. The difference in MADRS total score change from baseline to week 6 was statistically significant after multiplicity adjustment for CAR 1.5 mg/d vs PBO (-14.1 vs -11.5; adjusted P=.0050), but not for CAR 3 mg/d (-13.1; P=.0727). Differences for CAR 1.5 mg/d vs PBO were observed by week 2 (nominal P=.0453) and maintained at weeks 4 (nominal P<.0001) and 6 (nominal P=.0025). At week 6, more CAR 1.5 mg/d patients (44%) than PBO patients (34.9%) responded to treatment (nominal P=.0446). Greater improvement in the CGI-I scores was observed for CAR 1.5 (nominal P=.0026) and 3 mg/d (nominal P=.0076) vs PBO. At week 6, improvement in HAMD-17 total score reached nominal significance for CAR 1.5 mg/d vs PBO (-13.1 vs -11.1; nominal P=.0017), but not for CAR 3 mg/day (-12.2; P=.0783). HAM-A improvement was greater for CAR 1.5 mg/d vs PBO (nominal P=.0370). There were no deaths; 2 serious AEs occurred in each group (CAR: kidney infection, social stay hospitalization; PBO: depression, multiple sclerosis). The most common CAR AEs (≥5% and twice PBO) were akathisia and nausea.ConclusionCariprazine 1.5 mg/d was effective as adjunctive treatment in adults with MDD and inadequate response to ADT. Cariprazine was generally well tolerated, with a safety profile that was consistent with other indications. Together with results from a prior flex-dose study, these results suggest that adjunctive cariprazine may be an effective option for patients with inadequate response to ADT alone.FundingAbbVie

Cariprazine Use in Combination With a Mood Stabilizer in First Episode Mania.

BackgroundCariprazine's efficacy and safety have been previously tested in adult patients with acute mania associated with bipolar I disorder, but there is no available data in FEM. The objective of this study is to assess the efficacy and safety of cariprazine in combination with a mood stabilizer in treating FEM as well as to evaluate patients' adherence to the treatment.MethodsFEM patients were recruited from the acute inpatient unit at Lleida University Hospital Santa Maria, between January and June 2021. Their symptoms were evaluated using the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions–Severity (CGI-S) scale at admission and at discharge. Akathisia was assessed using the Barnes Akathisia Rating Scale. Patient adherence to medication treatment was assessed 30 days after discharge using the Morisky, Green and Levine Medication Adherence Scale. Socio-demographic and clinical information were further collected.ResultsEleven patients with FEM were involved, seven women and four men. Their mean age was 26.00+/-6.37 years. Mean hospitalization was 17.36+/−4.7 days. Cariprazine was combined with a mood stabilizer: lithium in seven patients and divalproex in four. Mean YMRS change from baseline was −24.55+/−7.5 and the mean CGI-S change from baseline was −2.55+/−0.82. Regarding adverse events, two (18.2%) patients presented with akathisia. At the 30-day treatment-adherence assessment, six (54.5%) patients were adherent and four (36.4%) had moderate adherence.ConclusionIn this sample, cariprazine in combination with mood stabilizers proved to be safe and effective in the treatment of FEM with more than half the patients being adherent to treatment. Therefore, cariprazine add-on is a good choice for promoting the long-term adherence of patients, thus minimizing the risk of relapse and improving prognosis.

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety.

Schizophrenia is characterized by positive, negative, cognitive, and affective symptoms. Antipsychotic medications, which work by blocking the dopamine D2 receptor, are the foundation of pharmacotherapy for schizophrenia to control positive symptoms. Cariprazine is a dopamine D3 receptor-preferring D3/D2 partial agonist antipsychotic that is approved for the treatment of schizophrenia (USA and European Union [EU]) and manic and depressive episodes associated with bipolar I disorder (USA). Partial agonist agents have a lower intrinsic activity at receptors than full agonists, so they act as either functional agonists or functional antagonists depending on the surrounding neurotransmitter environment. Beyond efficacy against positive symptoms, the unique D3-preferring partial agonist pharmacology of cariprazine suggests potential advantages against negative symptoms, and cognitive and functional impairment, which are challenging to treat. The efficacy and safety of cariprazine in adult patients with schizophrenia have been demonstrated in four short-term randomized, double-blind, placebo-controlled clinical trials, two long-term open-label studies, one relapse prevention study, and one prospective negative symptom study versus the active comparator risperidone. Additional post hoc investigations have supported efficacy across individual symptoms and domains in schizophrenia, as well as in diverse areas of interest including cognition, functioning, negative symptoms, hostility, and global well-being. This comprehensive review of cariprazine summarizes its pharmacologic profile, clinical trial evidence, and post hoc investigations. Collective evidence suggests that the pharmacology of cariprazine may offer broad-spectrum efficacy advantages for patients with schizophrenia, including effects against difficult-to-treat negative and cognitive symptoms, as well as functional improvements. Cariprazine was generally safe and well tolerated in patients with short- and long-term exposure and no new safety concerns were associated with longer-duration treatment.Trial registration ClinicalTrials.gov identifiers, NCT00404573, NCT00694707, NCT01104766, NCT01104779, NCT01412060, NCT00839852, NCT01104792.

The effectiveness and safety of cariprazine in schizophrenia patients with negative symptoms and insufficient effectiveness of previous antipsychotic therapy: an observational study.

The aim of the study was to examine the effectiveness and safety of cariprazine in routine psychiatric settings on schizophrenia patients with negative symptoms who have been treated with antipsychotics previously but without sufficient success. This was an open-label, flexible-dose, 16-week, observational study in Latvia. The primary outcome measure was an array of anamnesis-based clinical questions on schizophrenia symptoms rated on a seven-point scale. Other outcome measurements were the clinical global impression improvement (CGI-I) and severity (CGI-S) scales. Safety parameters included spontaneous reports of adverse events and specific assessments of extrapyramidal side-effects. A mixed model for repeated measures was fit to the data to evaluate the mean change from baseline for all visits. A total of 116 patients enrolled in the study (completion: 83%). Change from baseline to termination in symptom control was statistically significant (-7.3; P < 0.001), with the most improvement in negative symptoms (-6.3; P < 0.001). Over 70% of patients improved minimally or much based on the CGI-I scores at the final visit, and the CGI-S scores indicated an overall improvement in severity from moderately to mildly ill. 40% of patients experienced treatment-emergent adverse events. Over 70% of doctors were satisfied with the effectiveness and tolerability of cariprazine. Cariprazine significantly improved negative symptoms in schizophrenia patients.

The newer antipsychotic cariprazine (reagila): perspectives for use in different stages of schizophrenia therapy

Cariprazine is a newer 3rd generation antipsychotic acting as partial agonist for dopamine receptors with unique higher affinity for D3 than D2 receptors. This review article summarizes key data from preclinical and clinical studies of cariprazine including pharmacodynamics, pharmacokinetics, clinical efficacy and safety/acceptability in acute short-term and long-term maintenance and relapse prevention therapy in patients with schizophrenia. Efficacy and safety of cariprazine in patients schizophrenia with predominantly negative symptoms resistant to previous antipsychotic therapy is discussed as well.

Efficacy and Safety of Cariprazine in Acute Management of Psychiatric Disorders: a Meta-Analysis of Randomized Controlled Trials.

Cariprazine is a new atypical antipsychotic drug approved for the treatment of schizophrenia and bipolar disorders. we searched the published randomized controlled-trials (RCT) to review cariprazine efficacy and tolerability using the databases (PubMed, EUDRACT, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials) for cariprazine role in managing the following psychiatric conditions (schizophrenia, bipolar mania, bipolar depression and major depressive disorder). A meta-analysis was conducted using the identified 13 clinical trials to assess efficacy using with the outcomes: positive and negative syndrome scale (PANSS), clinical global impressions - severity of Illness (CGI-S), young mania rating scales (YMRS), Montgomery Asberg depression rating scale (MADRS) and Hamilton rating scale for depression (HAM-D). The risk of discontinuation due to adverse effects and common side effects were examined. The mean difference in change from baseline for PANSS was -6.23 (95% Confidence Interval (CI) -7.18, -5.28) favoring cariprazine treatment (p<0.00001). Similarly, mean difference for CGI-S was -0.36 (95% CI -0.41, -0.30), YMRS -5.64 (95% CI -6.86, -4.43), MADRS -1.43 (95% CI -1.88, -0.99) and HAM-D -1.52 (95% CI -2.28, -0.76). The risk ratio (RR) of discontinuing due to adverse events was 1.18 (95% CI 1.01, 1.38) meaning risk increased by 18% in cariprazine group with RR for EPS related side effects 2.82 (95% CI 2.47, 3.22) reflecting an increased risk of experiencing EPS related side effects by 182%. Cariprazine was also associated with an increased incidence of side effects such as akathisia, nausea and insomnia. Cariprazine demonstrates significant improvements in symptom intensity control in patients suffering from psychiatric conditions including schizophrenia, bipolar disorders and depression and is considered well-tolerated with similar rates of trials discontinuation; however, cariprazine was associated with a higher risk of EPS side effects. These findings will guide psychiatrists and pharmacists in their clinical role for supporting psychiatric patients care.

Efficacy and safety of cariprazine in the treatment of bipolar disorder

ABSTRACTIntroduction: Cariprazine, a D3-preferring, dopamine D2/D3 partial agonist, has efficacy in treating both acute phases of bipolar I disorder (BD-I). It has been approved by the FDA for treatment of acute manic, mixed and depressive episodes associated with BD-I.Areas covered: In this review, the authors discuss the unique pharmacological properties and clinical efficacy profile of cariprazine, and their relevance in the context of routine clinical decision-making for BD-I. For the purpose of this review, the authors searched for clinical trials in BD published in the PubMed, Web of Science, Embase and PsychInfo databases as well as for studies registered in the ClinicalTrials.gov database.Expert opinion: Based on evidence from RCTs in manic and mixed episodes, cariprazine in a dose-range of 3–12 mg is effective for treating acute mania and mixed states associated with BD-I. Importantly, evidence from placebo-controlled trials in bipolar depression suggests that cariprazine is also effective as a monotherapy in treating acute bipolar depression in doses of 1.5–3 mg/day. It is overall well tolerated; however, clinicians need to monitor patients for akathisia.

Cariprazine for the treatment of bipolar depression: a review

ABSTRACTIntroduction: Depressive symptoms and episodes dominate the course of bipolar disorder. The morbidity of bipolar disorder is disproportionately mediated by depressive symptoms; economic costs of bipolar disorder are also disproportionately due to unremitting depressive symptoms. Relatively few treatment options have established unequivocal efficacy in the treatment of bipolar depression. Herein we review evidence regarding the efficacy of the D3 preferring D2/D3 partial agonist cariprazine in the treatment of adults with bipolar depression.Areas covered: Randomized controlled trials that sought to determine the efficacy, tolerability, and safety of cariprazine in adults with bipolar I depression.Expert opinion: The available evidence from clinical trials indicates that cariprazine is effective at treating bipolar depression wherein treatment for bipolar depression remains an unmet need in bipolar disorder. Cariprazine has demonstrated good tolerability and safety profiles in bipolar disorder. Furthermore, cariprazine may be effective in improving both anhedonia and cognitive dysfunction. Long term prevention studies in bipolar depression, as well as separate studies evaluating efficacy in adults with bipolar II depression, are needed.

An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: A phase II, randomized clinical trial

IntroductionCariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania. This study (NCT00694707) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia. MethodsThis study was a multinational, double-blind, randomized, placebo- and active-controlled, fixed-dose trial. Patients were randomized to receive placebo, cariprazine 1.5mg/d, cariprazine 3.0mg/d, cariprazine 4.5mg/d, or risperidone 4.0mg/d (for assay sensitivity) for 6weeks of double-blind treatment and 2weeks of safety follow-up. Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total and Global Impressions-Severity of Illness (CGI-S) scores, respectively. Safety parameters included adverse events (AEs), vital signs, laboratory measures, and extrapyramidal symptom (EPS) scales. ResultsOf 732 randomized patients, 64% completed the study. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5mg/d, 3.0mg/d, and 4.5mg/d (least squares mean difference [LSMD]: −7.6, −8.8, −10.4, respectively; p<0.001; LOCF) and risperidone (−15.1, p<0.001; LOCF); significant improvement on CGI-S was demonstrated for all active treatments (p<0.05). The most frequent cariprazine AEs (≥5% and at least twice the rate of the placebo group) were insomnia, extrapyramidal disorder, akathisia, sedation, nausea, dizziness, and constipation. Mean changes in metabolic parameters were small and similar between groups. ConclusionThe results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.

EPA-0869 – Efficacy and safety of cariprazine in patients with acute manic or mixed episodes associated with bipolar I disorder

Cariprazine is a potent dopamine D 3 and D 2 receptor partial agonist with preferential binding to D 3 receptors. Summarize data from two Phase III, randomized, double-blind, placebo-controlled, flexible-dose, 3-week trials of cariprazine 3-12mg/d (NCT01058096) and cariprazine 3-6mg/d or 6-12mg/d (NCT01058668) in adults with bipolar I disorder and acute manic or mixed episodes. Evaluate the efficacy, safety, and tolerability of cariprazine in mania associated with bipolar I disorder. Primary and secondary efficacy parameters were change from baseline to Week 3 on the Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S), respectively, and were analyzed using a mixed-effects model for repeated measures. Randomized patient populations: 312 (NCT01058096; 154 placebo, 158 cariprazine 3–12mg/d) and 497 (NCT01058668; 161 placebo, 167 cariprazine 3–6mg/d, 169 cariprazine 6–12mg/d). Improvement from baseline to Week 3 on YMRS was significantly greater for each cariprazine group vs placebo ( P <0.001): least square mean difference (LSMD) was −4.3 (3–12mg/d), −6.1 (3–6mg/d) and −5.9 (6–12mg/d). For each cariprazine group, significantly more patients met YMRS response and remission criteria vs placebo. Cariprazine also was significantly superior to placebo on the CGI-S: LSMD was −0.4 (3–12mg/d, P =.0027), −0.6 (3–6mg/d, P <.001), −0.6 (6–12mg/d, P <.001). The only common cariprazine-related TEAEs (≥5% and twice rate of placebo) that occurred in both studies were akathisia and tremor. Changes in metabolic parameters were small and similar to placebo in both studies. Cariprazine was effective and generally well tolerated in the treatment of bipolar mania.

EPA-0870 – Efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia: results of two phase III trials

Introduction Cariprazine is a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. Objective Summarize data from 2 Phase III, randomized, double-blind (6-week), placebo-controlled trials of fixed-dose cariprazine (3mg/d and 6mg/d, NCT01104766) and flexible-dose cariprazine (3–6mg/d and 6–9mg/d, NCT01104779) in adults with acute exacerbation of schizophrenia. Aims Evaluate the efficacy, safety, and tolerability of cariprazine in schizophrenia. Methods Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions-Severity (CGI-S), respectively, and were analyzed using a mixed-effects model for repeated measures. Results Randomized patient populations: 617 (NCT01104766; 153 placebo, 155 cariprazine 3mg/d, 157 cariprazine 6mg/d, 152 aripiprazole) and 446 (NCT01104779; 147 placebo, 151 cariprazine 3–6mg/d, 148 cariprazine 6–9mg/d). Improvement from baseline to Week 6 on PANSS total scores was significantly greater with cariprazine vs placebo: least square mean difference (LSMD) was −6.0 (3mg/d, P=.0044), −6.8 (3–6mg/d, P=.0029), −8.8 (6mg/d, P Conclusion Cariprazine was effective and generally well tolerated in the treatment of schizophrenia.

P.3.d.008 Reproductive side effects of antipsychotic-induced hyperprolactinemia; a cross-sectional study – preliminary results

Cariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania. This study (NCT00694707) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.This study was a multinational, double-blind, randomized, placebo- and active-controlled, fixed-dose trial. Patients were randomized to receive placebo, cariprazine 1.5 mg/d, cariprazine 3.0 mg/d, cariprazine 4.5 mg/d, or risperidone 4.0 mg/d (for assay sensitivity) for 6 weeks of double-blind treatment and 2 weeks of safety follow-up. Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total and Global Impressions-Severity of Illness (CGI-S) scores, respectively. Safety parameters included adverse events (AEs), vital signs, laboratory measures, and extrapyramidal symptom (EPS) scales.Of 732 randomized patients, 64% completed the study. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5 mg/d, 3.0 mg/d, and 4.5 mg/d (least squares mean difference [LSMD]: − 7.6, − 8.8, − 10.4, respectively; p < 0.001; LOCF) and risperidone (− 15.1, p < 0.001; LOCF); significant improvement on CGI-S was demonstrated for all active treatments (p < 0.05). The most frequent cariprazine AEs (≥ 5% and at least twice the rate of the placebo group) were insomnia, extrapyramidal disorder, akathisia, sedation, nausea, dizziness, and constipation. Mean changes in metabolic parameters were small and similar between groups.The results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.

P.2.b.018 Post hoc analyses of levomilnacipran SR 40, 80, and 120 mg on functional outcomes in major depressive disorder

Cariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania. This study (NCT00694707) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.This study was a multinational, double-blind, randomized, placebo- and active-controlled, fixed-dose trial. Patients were randomized to receive placebo, cariprazine 1.5 mg/d, cariprazine 3.0 mg/d, cariprazine 4.5 mg/d, or risperidone 4.0 mg/d (for assay sensitivity) for 6 weeks of double-blind treatment and 2 weeks of safety follow-up. Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total and Global Impressions-Severity of Illness (CGI-S) scores, respectively. Safety parameters included adverse events (AEs), vital signs, laboratory measures, and extrapyramidal symptom (EPS) scales.Of 732 randomized patients, 64% completed the study. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5 mg/d, 3.0 mg/d, and 4.5 mg/d (least squares mean difference [LSMD]: − 7.6, − 8.8, − 10.4, respectively; p < 0.001; LOCF) and risperidone (− 15.1, p < 0.001; LOCF); significant improvement on CGI-S was demonstrated for all active treatments (p < 0.05). The most frequent cariprazine AEs (≥ 5% and at least twice the rate of the placebo group) were insomnia, extrapyramidal disorder, akathisia, sedation, nausea, dizziness, and constipation. Mean changes in metabolic parameters were small and similar between groups.The results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.

0471 TOLERABILITY AND SAFETY OF OLANZAPINE IN TWO SAMPLES OF ADOLESCENT AND YOUNG ADULT PATIENTS WITH PSYCHOSIS

Cariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania. This study (NCT00694707) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.This study was a multinational, double-blind, randomized, placebo- and active-controlled, fixed-dose trial. Patients were randomized to receive placebo, cariprazine 1.5 mg/d, cariprazine 3.0 mg/d, cariprazine 4.5 mg/d, or risperidone 4.0 mg/d (for assay sensitivity) for 6 weeks of double-blind treatment and 2 weeks of safety follow-up. Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total and Global Impressions-Severity of Illness (CGI-S) scores, respectively. Safety parameters included adverse events (AEs), vital signs, laboratory measures, and extrapyramidal symptom (EPS) scales.Of 732 randomized patients, 64% completed the study. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5 mg/d, 3.0 mg/d, and 4.5 mg/d (least squares mean difference [LSMD]: − 7.6, − 8.8, − 10.4, respectively; p < 0.001; LOCF) and risperidone (− 15.1, p < 0.001; LOCF); significant improvement on CGI-S was demonstrated for all active treatments (p < 0.05). The most frequent cariprazine AEs (≥ 5% and at least twice the rate of the placebo group) were insomnia, extrapyramidal disorder, akathisia, sedation, nausea, dizziness, and constipation. Mean changes in metabolic parameters were small and similar between groups.The results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia.